Bioresources and Bioprocessing
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2025
·Vol. 12
·期 1
·139
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IF 5.1
Jia Yan,Shi Yuxin,Wang Jie,Liu Honghui,Wang Hanyue,Huang Yilin,Liu Ya,Chen Peiyan,Peng Jie
Background Acute pancreatitis (AP) has caused great concern worldwide due to its serious threat to human health. Astragalin is a bioactive natural flavonoid compound with several pharmacological activities, but it remains unclear about its effect on AP. The objective of this experiment was to explore the mitigating efficacy of astragalin on caerulein-induced AP model and examine the underlying mechanisms. Methods Following the assessment of astragalin’s direct effects on pancreatic acinar cells using an in vitro AP model, an in vivo mouse model was established to further validate its efficacy and elucidate the underlying mechanisms. Pancreatic histopathology, amylase, and lipase levels of mice were observed to determine the optimal therapeutic dose of astragalin. The network pharmacology and RNA sequencing technology were used to reveal the possible targets and pathways. Subsequent molecular docking and western blot were conducted to validate the association between astragalin and key target molecules, as well as the NLRP3 signaling pathway. Combined with metagenomics and metabolomics analysis, the astragalin effective gut microbiota-metabolite-gene network was constructed. Moreover, fecal microbiota transplantation experiments were performed to clarify the importance of gut microbiota in astragalin-mediated alleviation of AP. Results The results showed that astragalin attenuated caerulein-induced injury in AR42J cells in vitro. Consistent with these findings, in vivo experiments revealed that astragalin treatment significantly improved pancreatic pathological injury, cell apoptosis, and systemic inflammatory response in AP mice, particularly at high doses. The integrated analysis of network pharmacology and transcriptomics revealed that the NLRP3 signaling pathway was a key molecular pathway, which was further validated using western blot. Docking analysis showed that 12 target genes had good docking activity with astragalin. More intriguingly, it was found that astragalin could reverse gut microbiota dysbiosis by restoring microbial diversity, altering bacterial community composition, and modulating key metabolic pathways. Specifically, astragalin-effective correlation networks were constructed with Lachnoclostridium sp. YL32, Roseburia intestinalis , Ruminococcus gnavus , Lachnospiraceae bacterium Choco86, Anaerobutyricum hallii , etc. as the core strains, 22 metabolites, including 5-Methoxytryptophan, D-Serine, L-Tryptophan, L-Methionine, etc. as core metabolites, and NLRP3 pathway-related genes as the main regulatory targets. Furthermore, fecal microbiota transplantation experiments confirmed the involvement of gut microbiota in AP remission. Conclusion Collectively, these findings identify astragalin as a promising therapeutic agent for AP, targeting both the NLRP3 signaling cascade and gut microbial homeostasis. Graphical
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TISSUE & CELL
·
2025
·
IF 2.5
Minhui Wang,Daojun Chen,Daofa Zhang,Hui Han,Maowei Xie,Ying Zhang,Yun Cao,Jiali Wei
Background Renal fibrosis (RF) is a common histopathological feature of chronic kidney disease (CKD) and is closely associated with persistent inflammation and regulated cell death. However, the underlying molecular mechanisms of pyroptosis in RF are unclear. Methods Pyroptosis-related hub genes in RF were identified through bioinformatics analysis. Granzyme B ( GZMB ) was knocked down in transforming growth factor (TGF-β)-stimulated HK-2 cells and in a folic acid (FA)-induced nephropathy mouse model. Western blot and enzyme-linked immunosorbent assays were performed to detect the expression of fibrosis and pyroptosis-related markers. Cell viability was assessed by the Cell Counting Kit-8 assay. Hematoxylin and eosin (HE) and Masson's staining were used to evaluate tubular injury and collagen deposition in renal tissues. Results GZMB was identified as a pyroptosis-associated hub gene. It was significantly upregulated in RF and exhibited high diagnostic performance. In TGF-β-stimulated HK-2 cells, GZMB knockdown enhanced cell viability and reduced lactate dehydrogenase release. In vivo , GZMB silencing ameliorated tubular injury, reduced collagen deposition, and improved renal function. The expression levels of pyroptosis-related proteins, including the N-terminal fragment of gasdermin D, cleaved caspase-1, and NOD-like receptor family pyrin domain containing 3 (NLRP3), as well as fibrotic markers alpha-smooth muscle actin and collagen type I, were downregulated after GZMB knockdown. Mechanically, GZMB knockdown inhibited NLRP3 inflammasome activation and suppressed the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. Conclusion GZMB deficiency inhibits pyroptosis and dampens the JAK2/STAT3 pathway, representing a potential approach for RF treatment.
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METABOLIC BRAIN DISEASE
·
2025
·Vol. 40
·期 8
·324
·
IF 3.5
Tian Lei,Su Pan,Feng Gang,Peng Shuaijun,Liu Liming,Yan Xiangli,Liu Xianghua,Li Yucheng,Bai Ming,Wang Baoying,Xu Erping
Modified Xiaoyao San (MXYS) is a well-established clinical prescription for the treatment of depression in China. While MXYS shows considerable promise for the development of new antidepressants, its pharmacological mechanisms remain poorly understood. This study aims to investigate the antidepressant potential and underlying mechanisms of MXYS in lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Behavioral assessments (sucrose preference test, tail suspension test, open field test) demonstrated that MXYS significantly ameliorated LPS-induced anhedonia and behavioral despair. Histopathological and molecular analyses revealed that MXYS mitigated LPS-induced neuronal damage in the prefrontal cortex (PFC), restored dendritic spine density, and rebalanced neuroinflammatory cytokines by reducing the pro-inflammatory IL-1β and elevating the anti-inflammatory IL-10. Moreover, MXYS promoted microglial polarization toward the anti-inflammatory M2 phenotype (CD206⁺) while suppressing the pro-inflammatory M1 phenotype (CD68⁺). Mechanistically, MXYS inhibited NLRP3 inflammasome activation and pyroptosis through the upregulation of the E3 ubiquitin ligase TRIM31, which facilitated NLRP3 degradation. Transmission electron microscopy confirmed that MXYS inhibited LPS-induced microglial pyroptosis, as evidenced by reduced Gasdermin D (GSDMD) expression and preserved cellular ultrastructure. In vitro validation using LPS-stimulated BV2 microglia further corroborated the MXYS-mediated suppression of NLRP3 inflammasome activity, pyroptosis, and inflammatory cytokine dysregulation, alongside enhanced TRIM31 expression. Collectively, these findings demonstrate that MXYS exerts antidepressant effects by modulating neuroinflammation through TRIM31-dependent NLRP3 ubiquitination, microglial phenotype switching, and the inhibition of pyroptosis, providing novel insights into its therapeutic potential for the treatment of depression. Graphical
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PHYTOMEDICINE
·
2025
·
IF 8.3
Huimin Li,Jingya Ruan,Jiayan Huang,Yijin Wu,Jiaming Cheng,Ongher Kouye,Yi Zhang,Tao Wang
Background Ulcerative colitis (UC) therapy remains challenging due to limited options. Pomegranate peel, rich in bioactive compounds, shows potential, but its key components and mechanisms underlying its action against UC are unclear. Purpose The present investigation was undertaken to assess the therapeutic efficacy of 70 % ethanolic (PPEE) and aqueous extracts (PPWE) derived from pomegranate peel, determine the primary active component, and clarify the underlying molecular mechanism. Study design and methods The anti-UC effects of PPEE and PPWE extracts were first assessed in DSS-induced mice. Differential constituents underlying their efficacy disparities were identified using LC-MS/UHPLC and chemometric analyses. Key bioactive compounds were screened via a model of Caco-2/THP-1 co-culture evaluating intestinal barrier function. The action mechanisms were further elucidated through molecular docking, surface plasmon resonance (SPR), co-immunoprecipitation (Co-IP), and other assays, validated across inflammatory cell models, DSS-induced mice, and human UC colon tissues. Results PPEE showed superior efficacy over PPWE, as evidenced by enhanced intestinal barrier function and suppressed inflammation and NLRP3 inflammasome activation. Ellagic acid (EA) was identified as the core active constituent, which directly targeted AKR1B1/AKR1B3, thereby inhibiting NLRP3-ASC oligomerization and subsequent cleavage of caspase-1 and IL-1 β . Conclusion This study unveils a novel pathogenic mechanism in UC, namely the AKR1B1/AKR1B3-NLRP3 axis, and identifies EA as its effective inhibitor. These results demonstrate the potential of pomegranate peel extracts and offer a novel therapeutic approach for UC.
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Journal of Inflammation Research
·
2025
·
IF 4.1
Jun Chen,Shengchen Ding,Huabing Yang,Yi Dai,Zhigang Zhang,Tianxiang Zhu,Lu Cao,Baifei Hu,Hongtao Liu
Purpose: Dihydromyricetin (DMY) is known for its wide range of pharmacological effects and has been approved as a dietary supplement. This study aimed to investigate the therapeutic effects of DMY on dextran sulfate sodium (DSS)-induced disruption of intestinal homeostasis in mice and to explore the underlying molecular mechanisms.Methods: To establish a model of colitis, mice were treated with a 3% DSS solution, followed by gavage administration of DMY for therapeutic intervention. Techniques such as histomorphology, RT-qPCR, 16S rRNA sequencing, and Western blot analysis were used.Results: DMY alleviated several physiological symptoms in colitis mice, including a reduction in the disease activity index (DAI) and spleen index, as well as decreases in the numbers of white blood cells, lymphocytes, and monocytes. Additionally, DMY helped repair the intestinal mucosal barrier function, reshaped the composition of gut microbiota, and regulated intestinal immune responses. These effects collectively contributed to the partial restoration of intestinal homeostasis in colitis mice. Furthermore, experiments with NLRP3−/− mice and pseudo-germ-free mice confirmed that DMY exerts its anti-colitis effects through the gut microbiota-NLRP3 inflammasome axis.Conclusion: DMY helps regulate intestinal homeostasis in colitis mice by suppressing the NLRP3 inflammasome via the gut microbiota. Our study provides new evidence supporting DMY as a potential therapeutic agent for colitis.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Gong Jing,Zhou Min,Huang Yue,Yu Mengjun,Zhou Qiang,Chen Shiwen,Wang Jia,Yang Min,Luo Qing,Zhang Rong,Huang Jingbin
Asthma is a chronic inflammatory respiratory disease worldwide. Its severe phenotypes, particularly the glucocorticoid-resistant ones, pose a major challenge, with neutrophilic inflammation being the key driver. However, no effective treatments are currently available. Herein, we report a macromolecular therapeutic strategy capable of targeting multiple key cells involved in the pathogenesis of neutrophilic asthma. The macromolecular therapy named PMART is constructed by conjugating artesunate and polyethylene glycol to the triazine scaffold. It is highly water-soluble and can self-assemble into nanomicelles, which enables efficient targeting to inflamed lung tissues and localization in inflammatory cells. In a murine model of neutrophilic asthma, PMART has proven to have in vivo efficacy equivalent to or greater than that of two clinically used anti-asthma drugs. Mechanistically, PMART reduces succinate levels by inhibiting branched-chain amino acid transaminase 1 (BCAT1) overexpression, thereby suppressing neutrophilic inflammation via blocking the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the production of pro-inflammatory cytokines. Notably, PMART exhibits a favorable safety profile in mice. Taken together, these data support the potential of PMART as a novel and highly effective therapeutic agent for neutrophilic asthma and other neutrophil-mediated diseases. Graphical
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Materials Today Bio
·
2026
·
IF 11
Chu Z,Yang T,Zhang Y,Zhu Q,Wang D,Tang H,Zhang G,Jiang M,Zhou L,Xu L,Fan T,Zhang J,Ma A,Xu C,Wang J,Tang H.
Ulcerative colitis (UC) remains a clinical challenge due to limited efficacy and side effects of conventional therapies, highlighting the need for novel interventions. Here, we investigate the therapeutic potential of naturally derived self-assembled nanoparticles (XDNPs) from the traditional Chinese medicine formula Xiexin Decoction (XXD) and rationally designed carrier-free nanoparticles (RBNPs) composed of berberine (BBR) and rhein. Both formulations effectively mitigated DSS-induced colitis by normalizing gut dysbiosis, reducing the release of pro-inflammatory mediators and facilitating macrophage phenotypic switching. Mechanistically, activity-based protein profiling identified VDAC1 as a direct functional target of BBR. Binding to VDAC1 inhibits its oligomerization, preventing the cytosolic release of oxidized mitochondrial DNA and subsequent activation of the NLRP3 inflammasome in macrophages. Co-assembly with rhein further enhances cellular uptake and bioavailability, amplifying anti-inflammatory efficacy. Proteomic and molecular analyses confirmed broad modulation of immune and metabolic pathways, while in vivo safety assessments demonstrated excellent biocompatibility without detectable organ toxicity. Collectively, this work elucidates a VDAC1-mediated mechanistic axis underlying the potent therapeutic effects of BBR-containing nanoparticles and establishes a rational nanomedicine strategy inspired by traditional herbal formulations. These findings provide a promising platform for the development of targeted, biocompatible nanotherapeutics for UC and other inflammatory disorders.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
Meng Zhang,Congyao Wang,Ruiqi Zhao,Jiabo Yuan
Background Asthma is a chronic disease characterized by airway remodeling, which results in a progressive decline in lung function. Senkyunolide A is one of the effective components of ligusticum chuanxiong Hort, it shows protective effects on many human diseases. However, the role of Senkyunolide A in asthma remains unclear. Results In our study, we established an asthma mouse model by ovalbumin (OVA) sensitization and challenge, and Senkyunolide A (20 mg/kg and 40 mg/kg) was given by intraperitoneal injection. For in vitro study, lung epithelial BEAS-2B cells were treated with TGF-β1 to induce epithelial mesenchymal transformation. Our study showed that Senkyunolide A (40 mg/kg) alleviated airway injury, inflammatory infiltration and airway remodeling induced by OVA in asthma mice. Meanwhile, Senkyunolide A (40 μM) recovered the high level of cell migration and profibrotic factors expression induced by TGF-β1. Mechanistically, Senkyunolide A abolished the effect of OVA or TGF-β1 on Smad2/3 phosphorylation at site Ser 465/467 /Ser 423/425 in mice or BEAS-2B cells and inhibited the activation of NLRP3 inflammasome induced by OVA. Conclusions In total, our study indicated that Senkyunolide A alleviated airway damage and airway remodeling in asthmatic mice and regulated the progress of asthma by inhibiting the TGF-β/Smad2/3 signaling pathway and NLRP3 activation.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
Xu Guobin,Wang Junlong,Gu Na,Yang Tiansong
Pyroptosis is a pathogenenic mechanism of polycystic ovary syndrome (PCOS). N5-methylcytosine (m5C) methylation is a RNA modification that affects the progression of diseases. However, its role in PCOS remains not understood. This study aimed to investigate the role of NSUN7 in PCOS, particularly its impact on pyroptosis. KGN cells were treated with LPS to establish a cell model, and pyroptosis was evaluated using enzyme-linked immunosorbent assay, flow cytometry, and western blotting. The effect of NSUN7 on the m5C modification of NLRP3 was assessed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and actinomycin D treatment experiment. A PCOS rat model was generated, hormones were detected using ELISA, and pyroptosis was evaluated in the ovaries and primary granulosa cells. The results showed that NSUN7 expression was reduced in patients with PCOS and LPS-treated KGN cells. Silencing of NSUN7 inhibited LPS-induced cell pyroptosis. Moreover, NSUN7 knockdown inhibited m5C methylation of NLRP3 and reduced NLRP3 mRNA stability. Overexpression of NLRP3 reversed the pyroptosis inhibition induced by NSUN7 knockdown. Furthermore, interfering with NSUN7 alleviated hormone abnormalities and suppressed granulosa cell pyroptosis in PCOS rats. In conclusion, silencing of NSUN7 attenuates PCOS progression by inhibiting pyroptosis of granulosa cells by suppressing m5C methylation of NLRP3.
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Molecular Medicine Reports
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2017
·Vol. 16
·期 6
·8413-8419
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IF 1.692
Qian An,Qian Hu,Bing Wang,Wenjun Cui,Fei Wu,Yu Ding
The overexpression of inflammasome components is correlated with diabetes‑associated complications. Oleanolic acid is a triterpenoid compound which is important in arterial injury. The present study evaluated whether oleanolic acid improved diabetic rat carotid artery injury through the inhibition of nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasomes signaling pathways. A diabetic rat model was induced using streptozotocin (60 mg/kg) and underwent carotid artery injury. Morphometric analysis was performed using hematoxylin and eosin staining. The mRNA and protein levels were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. It was found that oleanolic acid (100 mg/kg/day) improved body weight, glucose metabolic disorders, neointimal hyperplasia and endothelial dysfunction in diabetic rats with carotid artery injury. In addition, oleanolic acid administration significantly downregulated the mRNA and protein expression levels of endothelin 1 in diabetic rats. Oleanolic acid decreased the intimal area and the ratio of neointima to media in diabetic rats. Serum levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 in the oleanolic acid‑treated diabetic rats were downregulated. Consistent with the serum results, it was demonstrated that oleanolic acid administration caused a significant decrease in the levels of NLRP3, caspase‑1 and IL‑1β in the carotid arteries of diabetic rats. Taken together, these observations suggested that oleanolic acid attenuated carotid artery injury in diabetic rats and the underlying mechanism was mediated, at least partially, through the suppression of NLRP3 inflammasome signaling pathways.
研究领域:
药理学
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心血管疾病
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糖尿病
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Drug Design Development and Therapy
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2022
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IF 4.319
Hong Chen,Yongjie Ding,Wei Chen,Yun Feng,Guochao Shi
Background: Pulmonary fat embolism (PFE) is one of the important causes of acute lung injury (ALI), but its pathogenesis is unclear. In recent years, it has been found that the NLRP3 inflammasome is closely related to inflammatory response. However, there are no reports about the involvement of NLRP3 in PFE- associated ALI. Glibenclamide is a kind of hypoglycaemic drug with anti-inflammatory effect. It has been reported to have the anti-inflammatory effect related to inhibiting NLRP3.Objective: To determine whether NLRP3 inflammasome was involved in ALI induced by PFE or whether glibenclamide had therapeutic effects on such lung injury, we designed this experiment.Materials and methods: The rat model of intravenous injection of oleic acid (OA) was used to simulate PFE. Rats were divided into three groups: control, OA and glibenclamide treatment group. Blood free fatty acid (FFA) concentration was determined by ACS-ACOD. Histopathological examinations were taken to assess the severity of lung injury. The expression of NLRP3 pathway and its downstream products were analyzed by IHC, WB, qPCR and ELISA.Results: Four hours after intravenous OA injection, the typical pathological manifestations of ALI accompanied by elevated levels of plasma FFAs were found. The activity of NLRP3 inflammasomes increased in OA group, too. Pretreatment with glibenclamide partly inhibited the increase in NLRP3, caspase-1 and IL-1β expression induced by OA, simultaneously attenuated the lung injury. But it has little effect on the expression of Toll-like receptor 4 (TLR4) expression in this experiment.Conclusion: NLRP3 inflammasome, one of the main components of innate immune response, involved in ALI induced by OA. Glibenclamide can alleviate this kind of ALI by inhibiting rather the NLRP3/caspase-1/IL-1β signaling pathway than the levels of FFAs or TLR4 pathway.
研究领域:
药理学
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免疫学
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肺科学
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病理生理学
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Chinese Journal of Natural Medicines
·
2026
·Vol. 24
·期 4
·440-453
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IF 7.5
Zitong Zheng,Shang Lyu,Meijuan Wang,Peng Liu,Yashi Ou,Junfang Yi,Huajie Yang,Zengrui Liao,Jiangting Sun,Wei Zou,Yulin Feng
Gouty arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals in joint tissues. Pulchinenoside B4 (B4) has broad-spectrum anti-inflammatory properties, but its role and potential mechanism in the pathogenesis of GA are still unclear. The purpose of this study is to comprehensively elucidate the therapeutic effect and mechanism of B4 on GA by integrating transcriptome analysis and in vitro and in vivo experiments. In the MSU-induced mouse GA model, B4 treatment significantly improved ankle edema and reduced inflammatory cell infiltration. Through the analysis of transcriptome sequencing results, we identified multiple differentially expressed long non-coding RNAs (lncRNAs), such as Nod1 , Rbck1 and Pycard . In the in-depth exploration of the mechanism, we focused on the NOD-like receptor signaling pathway, NF- κ B signaling cascade, and B4-regulated macrophage polarization. In vitro and in vivo models, we confirmed that B4 significantly inhibited the expression and activation of key components of NLRP3 inflammasome (such as ASC, Caspase-1 and IL-1β) by qPCR, Western blot and immunofluorescence. Flow cytometry and immunofluorescence analysis further showed that B4 could prevent MSU-induced macrophage polarization to pro-inflammatory M1 phenotype. Based on these results, this study elucidated the mechanism of B4 improving MSU-induced GA inflammatory response by inhibiting NLRP3 inflammasome activation and blocking M1 macrophage polarization. These results suggest that B4 has great potential as a candidate drug for the treatment of GA.
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